The diseases caused by mycobacteria, primarily tuberculosis and leprosy, afflict over 40 million persons world-wide and are important economic, social, and medical burdens, particularly in the developing countries. It is the host's immune response to antigens of the invading mycobacteria that plays the key roles in determining the outcome and pathogenicity of an infection as well as forming the basis of procedures for the clinical detection of infection. The important, immunologically active mycobacterial antigens have not yet been well-defined. The long range goals of the proposed studies are to identify immunologically active mycobacterial proteins and to characterize their roles in the humoral, cellular, and protective immune responses to Mycobacterium tuberculosis. These studies should produce a clearer understanding of the immunologic composition of mycobacteria and hence a better understanding of the pathogenicity of, or immunity from, infection with M. tuberculosis. Also, by analyzing the immunologically active proteins at the molecular level, we may be able to produce reagents and procedures that might be useful for the clinical detection of tuberculosis. The basic approach will be to use antibodies and T-cells that are elicited during the course of an infection as the specific probes to identify recombinant DNA clones that express the immunologically active mycobacterial proteins in Escherichia coli. These recombinants then will be sources of individual mycobacterial proteins for studies to analyze their roles in the immune responses to infection and sources of mycobacterial genes for the detailed molecular analysis of these antigens. A key study here will be the definition of the mycobacterial antigens at the molecular level by an analysis of the immunogenicity and antigenicity of pieces of the proteins. The antibodies and antigens generated in these studies could be valuable reagents for the detection of tuberculosis.